Amiodarone is an investigational benzofuran derivative with known antianginal and antiarrhythmic effects. It has been shown to be effective in reducing the size of artificially induced myocardial infarct areas in the canine model and has been theorized but never proven to act in the blockade of the calcium mediated slow channel. This investigation was designed to test the possible protective effect of the drug on the hypertrophied myocardium during global ischemia under normothermic and hypothermic conditions in an isolated working heart model. Drug treated hearts differed significantly from controls in both normothermic (p Less than .00l) and hypothermic (p Less than .05) conditions by enhancing myocardial recovery of function (change in aortic output) after global ischemia. Amiodarone also significantly (p Less than .00l) enhanced survivability (restoration of aortic output and heart rate) in the normothermic drug treated group vs. controls. Hypothermic drug treated hearts had significantly (p Less than .05) enhanced recovery of function vs. normothermic drug treated hearts but differences between hypothermic control and normothermic controls were not significant (p Less than .l0) indicating possible synergy or addition between hypothermic and drug effects. It is concluded that Amiodarone ameliorated the deleterious effects of global ischemia in hypertrophied rat hearts at normothermic and moderately hypothermic temperatures.